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UHMK1 Is a Novel Marker for Personalized Prediction of Pancreatic Cancer Prognosis

Pancreatic ductal adenocarcinoma (PDAC) is among the leading causes of cancer mortality, and new therapeutic options are urgently needed. Long noncoding RNA H19 (H19) is known to promote PDAC progression, but the downstream genes of H19 are largely unknown. Five PDAC cell lines, nonmalignant pancrea...

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Autores principales: Luo, Yiqiao, Han, Shanshan, Yan, Bin, Ji, Huihui, Zhao, Lian, Gladkich, Jury, Herr, Ingrid
Formato: Online Artículo Texto
Lenguaje:English
Publicado: Frontiers Media S.A. 2022
Materias:
Acceso en línea:https://www.ncbi.nlm.nih.gov/pmc/articles/PMC8960145/
https://www.ncbi.nlm.nih.gov/pubmed/35359403
http://dx.doi.org/10.3389/fonc.2022.834647
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author Luo, Yiqiao
Han, Shanshan
Yan, Bin
Ji, Huihui
Zhao, Lian
Gladkich, Jury
Herr, Ingrid
author_facet Luo, Yiqiao
Han, Shanshan
Yan, Bin
Ji, Huihui
Zhao, Lian
Gladkich, Jury
Herr, Ingrid
author_sort Luo, Yiqiao
collection PubMed
description Pancreatic ductal adenocarcinoma (PDAC) is among the leading causes of cancer mortality, and new therapeutic options are urgently needed. Long noncoding RNA H19 (H19) is known to promote PDAC progression, but the downstream genes of H19 are largely unknown. Five PDAC cell lines, nonmalignant pancreatic cells, TCGA, GEO-derived pancreatic tissues (malignant, n=413; nonmalignant, n=234), a pancreatic tissue array (n=96), and pancreatic tissues from our clinic (malignant, n=20; nonmalignant, n=20) were examined by a gene array, RT-qPCR, Western blotting, MTT, colony formation, wound-healing, siRNA-mediated gene silencing, bioinformatics, xenotransplantation, and immunohistochemistry assays. The cell cycle inhibitor, UHMK1, was identified to have the strongest correlation with H19. UHMK1 expression was enhanced in PDAC, and high UHMK1 expression correlated with tumor stage, and lower overall survival. siRNA-mediated UHMK1 downregulation inhibited progression signaling. siRNA-mediated downregulation of H19 or UHMK1 inhibited tumor proliferation and xenograft growth. Based on the correlation between UHMK1 expression and clinical parameters, we developed a nomogram that reliably predicts patient prognosis and overall survival. Together, we characterized UHMK1 as an H19-induced oncogene and verified it as a novel PDAC prognostic marker for overall survival.
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spelling pubmed-89601452022-03-30 UHMK1 Is a Novel Marker for Personalized Prediction of Pancreatic Cancer Prognosis Luo, Yiqiao Han, Shanshan Yan, Bin Ji, Huihui Zhao, Lian Gladkich, Jury Herr, Ingrid Front Oncol Oncology Pancreatic ductal adenocarcinoma (PDAC) is among the leading causes of cancer mortality, and new therapeutic options are urgently needed. Long noncoding RNA H19 (H19) is known to promote PDAC progression, but the downstream genes of H19 are largely unknown. Five PDAC cell lines, nonmalignant pancreatic cells, TCGA, GEO-derived pancreatic tissues (malignant, n=413; nonmalignant, n=234), a pancreatic tissue array (n=96), and pancreatic tissues from our clinic (malignant, n=20; nonmalignant, n=20) were examined by a gene array, RT-qPCR, Western blotting, MTT, colony formation, wound-healing, siRNA-mediated gene silencing, bioinformatics, xenotransplantation, and immunohistochemistry assays. The cell cycle inhibitor, UHMK1, was identified to have the strongest correlation with H19. UHMK1 expression was enhanced in PDAC, and high UHMK1 expression correlated with tumor stage, and lower overall survival. siRNA-mediated UHMK1 downregulation inhibited progression signaling. siRNA-mediated downregulation of H19 or UHMK1 inhibited tumor proliferation and xenograft growth. Based on the correlation between UHMK1 expression and clinical parameters, we developed a nomogram that reliably predicts patient prognosis and overall survival. Together, we characterized UHMK1 as an H19-induced oncogene and verified it as a novel PDAC prognostic marker for overall survival. Frontiers Media S.A. 2022-03-10 /pmc/articles/PMC8960145/ /pubmed/35359403 http://dx.doi.org/10.3389/fonc.2022.834647 Text en Copyright © 2022 Luo, Han, Yan, Ji, Zhao, Gladkich and Herr https://creativecommons.org/licenses/by/4.0/This is an open-access article distributed under the terms of the Creative Commons Attribution License (CC BY). The use, distribution or reproduction in other forums is permitted, provided the original author(s) and the copyright owner(s) are credited and that the original publication in this journal is cited, in accordance with accepted academic practice. No use, distribution or reproduction is permitted which does not comply with these terms.
spellingShingle Oncology
Luo, Yiqiao
Han, Shanshan
Yan, Bin
Ji, Huihui
Zhao, Lian
Gladkich, Jury
Herr, Ingrid
UHMK1 Is a Novel Marker for Personalized Prediction of Pancreatic Cancer Prognosis
title UHMK1 Is a Novel Marker for Personalized Prediction of Pancreatic Cancer Prognosis
title_full UHMK1 Is a Novel Marker for Personalized Prediction of Pancreatic Cancer Prognosis
title_fullStr UHMK1 Is a Novel Marker for Personalized Prediction of Pancreatic Cancer Prognosis
title_full_unstemmed UHMK1 Is a Novel Marker for Personalized Prediction of Pancreatic Cancer Prognosis
title_short UHMK1 Is a Novel Marker for Personalized Prediction of Pancreatic Cancer Prognosis
title_sort uhmk1 is a novel marker for personalized prediction of pancreatic cancer prognosis
topic Oncology
url https://www.ncbi.nlm.nih.gov/pmc/articles/PMC8960145/
https://www.ncbi.nlm.nih.gov/pubmed/35359403
http://dx.doi.org/10.3389/fonc.2022.834647
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